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High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery

Not Applicable
Completed
Conditions
Congenital Heart Disease
Interventions
Procedure: Ultrafiltration
Registration Number
NCT04920643
Lead Sponsor
IWK Health Centre
Brief Summary

Malformations of the heart are common; 1.35 million infants are born each year with congenital heart disease. Many of these defects carry a considerable threat to the individual's quality of life as well as survival. Along with focused medical management, surgical repair remains a standard of care for more than 25,000 infants and children each year in the United States and Canada. The care of individuals with congenital heart disease is highly complex and has significant risks of morbidity and mortality. Most cardiac operations require the use of cardiopulmonary bypass (CPB, also known as the heart-lung machine) to safely access the inner chambers of the heart. CPB itself has been well documented to cause significant inflammation and hemodilution as the individual's blood is passed through a foreign circuit. This inflammatory response can lead to fluid overload, distributive shock and potential end-organ dysfunction in the heart, lungs, kidneys, brain, liver or bowels. These organ dysfunctions may culminate in post-operative low cardiac output syndrome (LCOS), prolonged ventilation time, prolonged intensive care unit (ICU) stay and can contribute to mortality.

Dampening the inflammatory response from CPB has been a focus of research interest for years. Intra-operative ultrafiltration has been used to remove excess fluids and filter off inflammatory cytokines during cardiac operations. Over 90% of children's heart centers in the world utilize some form of ultrafiltration (mostly some form of modified ultrafiltration), but there are wide variations in published ultrafiltration protocols (none of which are combination SBUF-SMUF in children). Ultimately, this project seeks to provide high-quality evidence that the immunologic and clinical effects of combination SBUF-SMUF are rate dependent. Therefore, a randomized study directly comparing a high-exchange SBUF-SMUF (60ml/kg/hr) and a low-exchange SBUF-SMUF (6ml/kg/hr) can identify which is the optimal ultrafiltration protocol to enhance post-operative clinical outcomes for this patient population. The expected data and results could be immediately applicable to improve recovery after heart surgery for infants and children across Canada and the rest of the world at large.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
104
Inclusion Criteria
  • Congenital heart patients (2.5 - 15kg) have consented for a planned cardiac surgery procedure requiring cardiopulmonary bypass.
  • Parent or legal substitute decision-maker informed written consent to participate in the study.
Exclusion Criteria
  • Patient or family refusal to participate.
  • Patient over 15kg (Fontan or Glenn patients will be considered up to 18kg)
  • No planned use of cardiopulmonary bypass
  • Isolated ASD repair
  • Known severe hematologic abnormality such as sick cell anemia, thalassemia, haemophilia A or B, von Willebrand disease or other.
  • Known genetic syndrome with severe neurologic or multi-organ abnormalities and immune dysfunction such as DiGeorge Syndrome, Trisomy 18 or 13, Noonan syndrome. (Trisomy 21 may be included in the study).
  • Known immunodeficiency syndrome or bone marrow pathology.
  • Severe liver or renal disease.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low-Exchange UltrafiltrationUltrafiltrationSubzero-Balance Simple Modified Ultrafiltration (6ml/kg/hour)
High-Exchange UltrafiltrationUltrafiltrationSubzero-Balance Simple Modified Ultrafiltration (60ml/kg/hour)
Primary Outcome Measures
NameTimeMethod
Peak Vasoactive-Ventilation Renal ScoreUp to 5 days
Secondary Outcome Measures
NameTimeMethod
Inotrope TimeUp to 28 days
Peak Oxygenation IndexUp to 5 days
Ventilation IndexUp to 5 days

Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.

Ventilator Free DaysUp to 28 days
Low Cardiac Output SyndromeUp to 3 days

Defined by any one of the following within the first 72 post-operative hours:

* Lactate \> 4mM with oxygen extraction \>35% (SaO2 - ScvO2/ SaO2)

* VIS \> 15.0 with oxygen extraction \>35% (SaO2 - ScvO2/ SaO2)

* Mechanical circulatory support requirement

Vasoplegic ShockUp to 3 days

Defined by any one of the following with the first 72 post-operative hours:

* Lactate \> 4mM with oxygen extraction \<25% (SaO2 - ScvO2/ SaO2)

* VIS \> 15.0 with oxygen extraction \<25% (SaO2 - ScvO2/ SaO2)

C-Reactive Protein ConcentrationsMeasured at 1 day
Vasoactive Inotrope ScoreUp to 5 days

Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.

Ventilation TimeUp to 28 days
Vasoactive-Ventilation Renal ScoreUp to 5 days

Taken in time series at ICU admission, 12, 24, 36, 48, 72, 96 and 120 hours.

Oxygenation IndexUp to 5 days

Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.

Inotrope Free DaysUp to 28 days
Cytokine Concentration (Patient Plasma)Up to 1 day

C3, C3a, C3b, C5, C5a, IL-1, IL1-Ra, IL-6, IL-10, TNF, CXCL-8 among others. The final selection of mediators will be subject to final pilot study results and assay availability. Taken at baseline, 0 hours and 24 hours after CPB.

LactateUp to 5 days

Measured by arterial blood gas (mM)

CreatinineUp to 5 days

Blood Concentration (uM)

Inotrope DependenceUp to 2 days

Vasoactive-inotrope score at 48 hours equal to or greater than that at ICU admission.

Loop Diuretic UseUp to 7 days

Total loop diuretic (mg/kg), measured in furosemide equivalents, during the first 7 post-operative days.

Peak Ventilation IndexUp to 5 days
Haptoglobin (Plasma)Up to 1 day
Complete blood countUp to 5 days
Composite Outcome of mechanical circulatory support, acute renal failure, prolonged intubation and operative mortality.Up to 30 days
Acute Kidney InjuryUp to 28 days

KDIGO Criteria

Peak Vasoactive-Inotrope ScoreUp to 5 days
Prolonged IntubationUp to 28 days

Mechanical ventilation for more than 7 days

ICU Length of StayUp to 30 days
Hospital Length of StayUp to 60 days

Trial Locations

Locations (1)

IWK Health Centre

🇨🇦

Halifax, Nova Scotia, Canada

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